Fluorinating agents which are site-selective toward organic, especially carbanionic substrates, are especially useful in preparing pharmacologically active compounds. A number of electrophilic fluorinating agents are known but have enjoyed only limited commercial success because they are expensive, difficult to handle and sometimes provide insufficient selectivity. Nevertheless, the many advantages associated with using fluorine chemistry to regiospecifically introduce fluorine atoms into complex organic compounds and the unique properties of the fluorine-containing organic compounds obtained therefrom has led to a considerable effort to develop improved fluorination processes.
The Balz-Schiemann reaction constitutes the classical method of introducing fluorine onto an aromatic ring wherein an aromatic amine functionality situated on an aromatic ring is replaced by fluorine. A fluorine atom can be introduced into a wide range of organic compounds by diazotization of a corresponding aromatic amine in the presence of tetrafluoroboric acid. A review of the reaction as well as other methods for preparing fluoroaromatic compounds in presented in Aldrichimica Acta, 21 (1988) 3.
Known electrophilic fluorinating reagents include fluorine solutions in halogenated or other suitable solvents at low temperature (e.g., -78.degree. C.) trifluoromethyl hypofluorite (CF.sub.3 OF), cesium fluoroxysulfate (CsSO.sub.4 F) and perchloryl fluoride (FClO.sub.3). A review of these electrophilic fluorinating agents is presented in S. T. Purrington, et al, Chem Rev., 86 (1986), 997 and G. G. Furin, "New Fluorinating Agents in Organic Synthesis". Xenon difluoride (XeF.sub.2) is potentially less hazardous but is too expensive to justify its use in many applications.
Attention has recently been directed to using compounds of the N-F class, i.e., having an N-F bond, as electrophilic fluorinating agents. The prototypical member of this class is perfluoro-N-fluoropiperidine (R. E. Banks and G. E. Williamson, Chem. Ind. [London], 1964 and R. E. Banks, et al., J. Chem. Soc., Perkin Trans. I, [1972], 1098). However, this compound is obtainable only in low yields by electrochemical fluorination of either pyridine (about 8% yield) or 2-fluoropyridine (about 13%) in anhydrous hydrogen fluoride. Furthermore, this reagent is inadequately active in several applications, and, on transfer of fluorine to a carbanionic substrate, may liberate imidoyl fluoride perfluoro-1-azacyclohex-1-ene which then competes with the electrophilic fluorine source for the substrate. Similar problems militate against using analogous compounds such as perfluoro-(N-fluoro-2,6-dimethylpiperidine) and perfluoro-N-fluoromorpholine, (R. E. Banks, et al., J. Chem. Soc. Perkin Trans. I [1988], 2805) and poly[perfluoro-(N-fluoropiperidin-4-ylethylnene)](R. E. Banks, et al, J. Fluorine Chem., [1986], 34 281) as electrophilic fluorinating agents.
U.S. Pat. No. 4,828,764 discloses electrophilic fluorinating agents having the structure of N-fluoro-N-perfluoroalkyl or perfluoroaryl sulfonamides represented by the formula RfSO.sub.2 NFR wherein Rf represents a perfluorinated C.sub.1 -C.sub.30 alkyl, C.sub.3 -C.sub.30 cycloalkyl, C.sub.6 -C.sub.14 aryl substituted C.sub.1 -C.sub.10 alkyl or a C.sub.6 -C.sub.14 aryl group and R represents a C.sub.1 -C.sub.30 alkyl, C.sub.3 -C.sub.30 cycloalkyl, C.sub.6 -C.sub.14 aryl substituted C.sub.1 -C.sub.10 alkyl, or C.sub.6 -C.sub.14 aryl group optionally substituted with one or more inert substituents including fluorine. When Rf is trifluoromethyl, R may alternatively be represented by a perfluoromethyl sulfonamido group. Preferred fluorinating agents are N-fluorobis-(trifluoromethanesulfon)imide (Rf=CF.sub.3 and R=CF.sub.3 SO.sub.2) and N-fluoro-N-methyl-trifluoromethanesulfonamide (Rf=CF.sub.3 and R=CH.sub.3). The former compound (also known as the DesMarteau reagent) is a powerful electrophilic fluorinating agent which is capable of fluorinating benzene to fluorobenzene at room temperature but is tedious to prepare requiring eight or nine reactions steps from readily available material.
U.S. Pat. No. 5,086,178, assigned to Air Products and Chemicals, Inc., Allentown, Pa., discloses various electrophilic fluorinating agents of the N-F class and provides novel fluorinated diazabicycloalkane derivatives, methods for their preparation and their use as fluorinating agents. A representative derivative is 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane ditriflate.
Considerable commerical interest exists in discovering an effective electrophilic fluorinating process capable of regiospecifically introducing a fluorine atom at a position ortho to a desired substituent situated on an aromatic compound wherein the reagents are stable, relatively inexpensive and readily obtainable from presently commercially available starting materials.